来自一项关于注射用促肾上腺皮质激素（Acthar® Gel）治疗持续活动系统性红斑狼疮的4期、多中心、随机、双盲、安慰剂对照试验的事后生物标志物分析。
Post Hoc Biomarker Analyses from a Phase 4, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Repository Corticotropin Injection (Acthar® Gel) for Persistently Active Systemic Lupus Erythematosus.
作者信息
Askanase Anca D, Wright Dale, Zhao Enxu, Zhu Julie, Bilyk Roman, Furie Richard A
机构信息
Columbia University Medical Center, 630 West 168th Street, P&S 3-3450, New York, NY, 10032, USA.
Mallinckrodt Pharmaceuticals, Hampton, NJ, USA.
出版信息
Rheumatol Ther. 2021 Dec;8(4):1871-1886. doi: 10.1007/s40744-021-00351-7. Epub 2021 Sep 3.
INTRODUCTION
We conducted post hoc analyses of biomarker results from a multicenter, randomized, double-blind, placebo-controlled study of repository corticotropin injection (RCI; Acthar® Gel) in patients with persistently active systemic lupus erythematosus (SLE) despite treatment with moderate-dose glucocorticoids.
METHODS
Adults with active SLE and moderate to severe rash and/or arthritis were enrolled in the primary study. Patients had active SLE despite treatment with stable glucocorticoids, antimalarials, and nonsteroidal anti-inflammatory drugs and/or immunosuppressants. Patients were randomly assigned to 80 U of RCI or placebo subcutaneously every other day for 4 weeks and then twice weekly through week 24. Blood samples were analyzed for serum cytokines and complement proteins using enzyme-linked immunosorbent or Luminex assays and for circulating leukocytes using flow cytometry. Biomarker levels were reported as percentages of the baseline and were further evaluated in subgroups stratified by baseline SLE Disease Activity Index-2000 (SLEDAI-2K) scores (< 10 vs. ≥ 10), baseline anti-double-stranded DNA levels (< 15 IU/mL vs. ≥ 15 IU/mL), and BILAG-based Combined Lupus Assessment (BICLA) responses at week 20 and 24.
RESULTS
RCI treatment resulted in reduced levels of B cell-activating factor and interleukin-6 cytokines in all subgroups compared with placebo. RCI treatment also resulted in lower levels of CD19 B cells and CD19IgDCD27CD95 atypical activated memory B cells than did placebo in the higher baseline disease activity subgroups and in BICLA non-responders. Furthermore, RCI treatment led to greater increases in complement component (C)3 and C4 levels than did placebo in the higher baseline disease activity subgroups and in BICLA responders.
CONCLUSIONS
RCI may reduce inflammation through B cell immunomodulation in patients with persistently active SLE, particularly in those with higher disease activity.
TRIAL REGISTRATION
ClinicalTrials.gov identifier NCT02953821.
简介
我们对一项多中心、随机、双盲、安慰剂对照研究的生物标志物结果进行了事后分析，该研究针对的是尽管接受了中等剂量糖皮质激素治疗但仍患有持续性活动性系统性红斑狼疮（SLE）的患者，使用的药物是储存促肾上腺皮质激素注射液（RCI；Acthar® Gel）。
方法
患有活动性SLE且有中度至重度皮疹和/或关节炎的成年人被纳入主要研究。尽管接受了稳定的糖皮质激素、抗疟药、非甾体抗炎药和/或免疫抑制剂治疗，但患者仍患有活动性SLE。患者被随机分配，每隔一天皮下注射80 U的RCI或安慰剂，持续4周，然后每周两次，直至第24周。使用酶联免疫吸附或Luminex检测法分析血样中的血清细胞因子和补体蛋白，并使用流式细胞术分析循环白细胞。生物标志物水平以相对于基线的百分比报告，并在按基线SLE疾病活动指数-2000（SLEDAI-2K）评分（<10 vs.≥10）、基线抗双链DNA水平（<15 IU/mL vs.≥15 IU/mL）以及第20周和24周基于BILAG的联合狼疮评估（BICLA）反应分层的亚组中进行进一步评估。
结果
与安慰剂相比，RCI治疗导致所有亚组中的B细胞活化因子和白细胞介素-6细胞因子水平降低。在基线疾病活动较高的亚组和BICLA无反应者中，RCI治疗导致的CD19 B细胞和CD19IgDCD27CD95非典型活化记忆B细胞水平也低于安慰剂。此外，在基线疾病活动较高的亚组和BICLA反应者中，RCI治疗导致补体成分（C）3和C4水平的升高幅度大于安慰剂。
结论
RCI可能通过对持续性活动性SLE患者的B细胞进行免疫调节来减轻炎症，尤其是在疾病活动较高的患者中。
试验注册
ClinicalTrials.gov标识符NCT02953821。
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